The aim of this project is to increase our knowledge of the mechanisms controlling ionic conductance of postsynaptic membranes at a neuronal synapse. The specific objectives for this grant period are: a. The characterization of receptor-channel kinetics of the cholinergic, nicotinic receptor at sympathetic postganglionic neurons. b. The identification of the rate limiting process which determines the decay of the fast EPSC at sympathetic postganglionic neurons. An important approach toward understanding the molecular mechanisms controlling chemically gated conductance changes involves studies of transmitter-receptor kinetics. This approach has been successfully used to characterize the interaction between acetylcholine and its receptor on the postjunctional membrane at the motor end-plate of skeletal muscle (Magleby and Stevens, 1972a, b). A careful characterization of transmitter-receptor kinetics of the fast EPSC in the sympathetic ganglion will provide a basic description of a chemically gated conductance in a neuronal synapse. These results can then be compared to those obtained previously in studies of receptor kinetics in skeletal muscle. Our initial observations suggest that the gating mechanism may have quite different properties in ganglion cells. The methods to be utilized (voltage clamp analysis of synaptic currents and current fluctuations during iontophoretic agonist application) represent the most sophisticated tools presently available. Consequently, the information obtained should provide additional important information concerning the control of synaptic conductance at neuronal synapses.